- Biogen Inc. spooked investors Wednesday with news it would increase enrollment into two Phase 3 studies testing the biotech's all-important Alzheimer's disease candidate aducanumab due to "variability" on the primary endpoint.
- Shares in Biogen slid in value by about 6.6% on the update, which was disclosed during a conversation with the company's Chief Medical Officer Al Sandrock at a conference hosted by the investment bank Leerink Partners LLC.
- What exactly Biogen observed in its blinded check of the studies is not entirely clear. In light of the unexpected variance though, Biogen will add about 255 patients to each of the aducanumab studies in order to maintain sufficient statistical power to detect a significant difference between treatment and placebo.
Investors still bullish on the prospect of pharma ever developing a drug for Alzheimer's could be excused some jitters this week. Biogen's anxiety-inducing update on the two Phase 3 studies testing aducanumab came just a day after Merck & Co. pulled the plug on a late-stage study of its Alzheimer's drug verubecestat.
While confidence in Merck's drug was low after a previous study failed to show any signs of efficacy, the announcement added to the long list of clinical setbacks in Alzheimer's.
The comments from Biogen's Sandrock sparked more hand wringing on Wall Street, however, as it involved aducanumab — the current standard bearer for the industry's hopes of finding a disease-modifying drug for the neurodegenerative disease.
Like other high-profile (but failed) drugs before it, aducanumab targets the clumps of protein known as amyloid plaques that are thought to be a potential cause or symptom of the disease.
Biogen is currently testing aducanumab in two large Phase 3 studies, called ENGAGE and EMERGE, that are expected to read out data in 2020.
Under the studies' protocol, Biogen had designed a pre-planned check to re-estimate the sample sizes needed to ensure a 90% chance of avoiding a false negative result.
"We did see more variability on the primary endpoint than assumed when we did the original sample size estimations," explained Sandrock to the investor audience at Leerink's conference in New York this week. "So we've decided to increase the sample size to maintain 90% power."
Sandrock emphasized that the studies remained blinded and that the sample size re-estimation did not change Biogen's confidence in aducanumab.
Still, the news caused some confusion and uncertainty — partly due to the vague phrasing of "variability" and partly perhaps because the news emerged from comments at a conference rather than a press release or regulatory filing.
Analysts were less concerned than markets, however.
"While we understand the easier-to-see negative interpretation (and the points are well taken), there is also a neutral/positive and very realistic one on several levels that we believe may be getting overlooked," wrote Mizuho Securities USA LLC analyst Salim Syed in a Feb. 15 note.
Syed suggested the upsizing of the trial could be seen as a result of "smart trial design" by Biogen, allowing for room to expand the study in case its original assumptions proved off the mark.
Another factor shoring up confidence were comments by Biogen's Sandrock that enrollment into the study was proceeding "briskly," with fewer drop outs than expected. A lower drop out rate could be a sign physicians or patients saw some signs of benefit (or at least weren't seeing an adverse events to prompt discontinuation).
Biogen expects to complete enrollment by mid-summer this year. Since the studies test change from baseline in cognitive scores over 18 months, results should come in late 2019/early 2020.